Field
The present disclosure relates to compositions and methods for preparing dried powders, more specifically to methods for preparing dried powders of pharmacologically active compositions.
Related Art
Proteins, hormones, antibodies, vaccines, blood plasma, and other fragile molecules stored as aqueous solutions have short shelf lives. They must be refrigerated (typically maintained in an environment of 2 to 8° C.). Even under the best of circumstances, many solution-based formulations exhibit a protein concentration loss over time, which is presumably due to the formation of dimers and other protein aggregates in solution. Such formulations frequently must be supplemented with stabilizing additives such as buffers and/or antioxidants to minimize solution instability.
By removing the water from the material, such products may be easily stored for longer durations. Once dried, such material can be shipped and later reconstituted to its original active form for injection. Since many of these materials are heat-sensitive and require special care during the drying process, formulations of these materials frequently must be supplemented with stabilizing additives such as buffers and/or antioxidants to minimize solution instability in addition to other excipients.
Lyophilization is often used to dry these fragile substances. Lyophilization works by freezing the material and then reducing the surrounding vapor pressure to allow the frozen water in the material to sublimate directly from the solid phase to the gas phase. A very low operating temperature avoids damaging these heat-sensitive products; however, it is a slow expensive process, requiring costly equipment and considerable energy. In addition, solutions of such products must be supplemented with cryoprotectants to minimize the damage caused by freezing. Such formulation development is time consuming and expensive.
Lyophilized powders are typically formed as cakes; in many cases requiring additional grinding and milling and optionally sieving processing in order to create flowing powders. In the past few years, spray drying has been employed as an alternative approach for preparing a number of therapeutic protein-based powders. Unfortunately, certain proteins, hormones, antibodies, and cytokines in particular, are prone to degradation during spray drying, and loss of their secondary structure, due to heat.
Thus, there remains a need for an improved method for preparing dried powders of biologically active compositions, which provides dried material that maintains its biological activity for a long time at low economic cost.